Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency.

Background: A well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed. Methods: Whole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 'Kaleidoscope' scores were recorded. Vaccine responses were scored from zero to three. Results: 99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41). Conclusions: Covid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.

Oro-Naso-Sino-Orbital-Cutaneous Fistula From Prolonged Cocaine Use.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

A Comparison of the Performance of SARS-CoV-2 Antibody Assays in Healthcare Workers with COVID-19.

Aims Since its emergence, significant interest surrounds the use of SARS-CoV-2 serological tests as an alternative or as an adjunct to molecular testing. However, given the speed of this pandemic, paralleled with the pressure to develop and provide serological tests in an expediated manner, not every assay has undergone the rigorous evaluation that is usually associated with medical diagnostic assays. We aimed to examine the performance of several commercially available SARS-CoV-2 IgG antibody assays among participants with confirmed COVID-19 disease and negative controls. Methods Serum taken between day 17 and day 40 post onset of symptoms from 41 healthcare workers with RT-PCR confirmed COVID-19 disease, and pre-pandemic serum from 20 negative controls, were tested for the presence of SARS-CoV-2 IgG using 7 different assays including point-of-care (POC) and laboratory-based assays. Results Assay performance varied. The lab-based Abbott diagnostics SARS-CoV-2 IgG assay proved to be the assay with the best positive and negative predictive value, and overall accuracy. The POC Nal von Minden GmbH and Biozek assays also performed well. Conclusion Our research demonstrates the variations in performance of several commercially available SARS-CoV-2 antibody assays. These findings identify the limitations of some serological tests for SARS-CoV-2. This information will help inform test selection and may have particular relevance to providers operating beyond accredited laboratories.

Leukocyte Adhesion Deficiency Type 1 Due to Novel ITGB2 Mutation.

Aim Marked neutrophilia and omphalitis in an infant resulted in the diagnosis of the first case of leukocyte adhesion deficiency type 1 (LAD1) in Ireland. Diagnosis LAD1 requires specific molecular diagnostics for its correct identification. Results Early identification of this disorder allowed for rapid referral for haemotopoeitic stem cell transplant which has resulted in an excellent outcome for this patient. Conclusion The identification of a previously unknown ITGB2 mutation resulting in LAD1 in Ireland should alert physicians to the diagnostic possibility of this extremely rare disorder.

The effect of a low-dose naloxone infusion on the incidence of respiratory depression after intrathecal morphine administration for major open hepatobiliary surgery: a randomised controlled trial.

Intrathecal morphine is an analgesic option for major hepatopancreaticobiliary procedures but is associated with a risk of respiratory depression. We hypothesised that a postoperative low-dose naloxone infusion would reduce the incidence of respiratory depression without an increase in pain scores. Patients scheduled for major open hepatopancreaticobiliary surgery and who were receiving 10 µg.kg-1 intrathecal morphine were eligible for inclusion. Patients were allocated randomly to receive a postoperative infusion of naloxone 5 µg.kg-1 .h-1 (naloxone group) or saline at an identical infusion rate (control group) until the morning after surgery. Clinicians, nursing staff and patients were blinded to group allocation. The primary outcome measure was the incidence of respiratory depression (respiratory rate < 10 breaths.min-1 and/or oxygen saturation < 90%). Secondary outcome measures included: arterial partial pressure of carbon dioxide; pain score; requirement for supplemental analgesic; and incidence of nausea and vomiting, pruritus and sedation. In total, data from 95 patients (48 in the naloxone group and 47 in the control group) were analysed. The incidence of respiratory depression was lower in the naloxone group compared with the control group (10/48 vs. 21/47 patients, respectively; p = 0.037, relative risk 0.47 (95%CI 0.25-0.87). Maximum pain scores were greater for patients allocated to the naloxone group compared with control (median 5 (95%CI 4-6) vs. 4 (95%CI 2-4), respectively; p < 0.001). A low-dose naloxone infusion decreases the incidence of respiratory depression following intrathecal morphine administration in patients having major hepatopancreaticobiliary surgery at the expense of a small increase in postoperative pain.

Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury.

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.

Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial.

The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46-2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40-2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22-2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15-2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals.

Predictors of outcome in decompensated liver disease: validation of the SOFA-L score.

A growing number of patients with liver disease are being referred for critical care support. We have recently shown that a combination of lactate and SOFA score (SOFA-L score) may provide an accurate, objective measurement of prognosis in a group of patients admitted to ICU with alcoholic liver disease. This score has not been validated in an independent patient cohort. A retrospective study was performed where patients admitted to our ICU with decompensated liver disease (any cause) were included. The SOFA-L score accurately predicted in-hospital mortality in this group of patients with an area under the ROC curve of 0.83. Sensitivity and specificity were 65% and 87% respectively SOFA-L performed superior to SOFA, MELD and MELD-Na scores. This study validates the use of the SOFA-L score in the initial 24 hours of ICU admission as an accurate predictor of mortality in this group of patients with a high mortality.

Utility of near infrared light to determine tissue oxygenation during hepato-biliary surgery.

Near-infrared spectrophotometry assesses cerebral oxygen saturation (ScO2) based on the absorption spectra of oxygenated and deoxygenated hemoglobin, and the translucency of biological tissue, in the near-infrared band. There is increasing evidence that optimising cerebral oxygenation, guided by ScO2, is associated with improved outcomes in a variety of high risk surgical settings. However, in patients with liver disease, bilirubin can potentially render cerebral oximetry inaccurate. As a result, measurement of cerebral oxygen saturation is rarely undertaken in patients undergoing hepatobiliary surgery. We prospectively measured baseline and intraoperative cerebral oxygen saturation in patients undergoing major pancreatic surgery. Indices including bilirubin, sodium, platelets and maximum amplitude on thromboelastography were associated with low baseline ScO2. However, those patients with low ScO2 (≤51%) maintained a similar trend in cerebral oximetry values both at induction and intraoperatively to those with a normal ScO2. We conclude that the pattern of cerebral oximetry is similar in patients undergoing major pancreatic surgery regardless of their underlying liver dysfunction. Therefore, cerebral oximetry may have a role in monitoring neurological function in this high risk group of patients.

Allergy in Irish adults: a survey of referrals and outcomes at a major centre.

BACKGROUND: There is an increasing demand for specialist public allergy services across Ireland. Little data exist on the patterns of allergic disease in Irish adults. The limited resources available require innovative strategies to ensure quality care delivery. AIMS: This study aimed to review the types of allergy referrals and diagnostic outcomes at a major Irish centre, and to establish an efficient method of communication with non-specialist practitioners. METHODS: Demographic data, referral characteristics and diagnostic outcomes from one hundred consecutive new allergy referrals were identified. Additionally, communications to a pilot email service were reviewed over a 12-month period and user satisfaction assessed. RESULTS: Requests for the investigation of food allergy accounted for 71% of referrals. Despite this, the main diagnostic outcome in this cohort was a non-allergic condition, chronic spontaneous urticaria (56%). immunoglobulin E (IgE)-mediated food allergy was definitively diagnosed in only 9% of patients, with the majority of these presenting with anaphylaxis. The allergy advice email service received 43 requests for assistance over 12 months, mainly for help in the interpretation of an allergy clinical history. Feedback on the email service was universally positive. CONCLUSIONS: The majority of patients in this cohort did not have IgE-mediated allergic disease. Increased awareness of the features that differentiate allergy from non-allergic conditions such as food intolerance or chronic spontaneous urticaria is required. The allergy advice email service should be developed further to play a key role in education and care delivery in partnership primary care.

Alcoholic liver disease in the intensive care unit: outcomes and predictors of prognosis.

BACKGROUND: An increasing number of patients with alcoholic liver disease (ALD) are being referred for critical care support, but limited information is available on their short- and medium-term outcomes. This study aimed to determine mortality rates, identify optimal predictors of prognosis, and determine the appropriate time to apply these predictors in patients with ALD admitted to intensive care unit (ICU). METHODS: In this retrospective study, patients admitted to ICU between 2009 and 2012 with a primary diagnosis of ALD were included. Survival was calculated using the Kaplan-Meier method, risk factors for death determined by logistic regression analysis, and discriminative capacity of models using receiver operating characteristic curves. RESULTS: Of 170 patients admitted with liver disease, 62 met the inclusion criteria. Survival rates in the ICU, in hospital, and at 6 months were 40.3% (95% confidence interval [CI], 30.7%-49.9%), 35.5% (95% CI, 25.35%-45.65%), and 29% (95% CI, 19.4%-38.6%), respectively. Multiple linear regression analysis of day 1 variables produced an equation with Sequential Organ Failure Assessment score and lactate as significant predictors of mortality; this model had an area under the receiver operating characteristic curve of 0.93. A score greater than 12 in this model correlated with a mortality of more than 80% at all time points and was more accurate than any other score examined. CONCLUSION: Patients admitted to ICU with ALD have a very high inhospital mortality. A combination of the established Sequential Organ Failure Assessment score and lactate provided the most accurate predictor of outcome on day of admission and at all subsequent time points.

The United Kingdom Primary Immune Deficiency (UKPID) Registry: report of the first 4 years' activity 2008-2012.

This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University College, London. It is accessible to users through the website of the United Kingdom Primary Immunodeficiency Network (www.ukpin.org.uk). Twenty-seven centres in the United Kingdom are actively contributing data, with an additional nine centres completing their ethical and governance approvals to participate. This indicates that 36 of 38 (95%) of recognized centres in the United Kingdom have engaged with this project. To date, 2229 patients have been enrolled, with a notable increasing rate of recruitment in the past 12 months. Data are presented on the range of diagnoses recorded, estimated minimum disease prevalence, geographical distribution of patients across the United Kingdom, age at presentation, diagnostic delay, treatment modalities used and evidence of their monitoring and effectiveness.

Should we stop doing blind transversus abdominis plane blocks?

BACKGROUND: Any landmark-based regional anaesthetic technique raises two important issues. The first is the accuracy of placement of the needle and thus the local anaesthetic in a 'blind' technique and the second is the potential for damage to adjacent structures. We designed a prospective, blinded study in an adult general surgical population to evaluate with ultrasound the placement of the needle tip and local anaesthetic during transversus abdominis plane (TAP) blocks using the landmark-based 'double-pop' technique. METHODS: After induction of general anaesthesia, 36 adult patients had a TAP block performed bilaterally using the standard landmark-based technique. Ultrasonography was then used to record the actual needle position and local anaesthetic spread. The anaesthetist performing the block was blinded to the ultrasound images. RESULTS: Thirty-six adult patients were included in the study, which was terminated early due to what was considered an unacceptably high level of peritoneal needle placements. The needle tip and local anaesthetic spread were in the correct plane in only 17 (23.6%) of the injections. In the remaining 55 (76.4%), the needle was in the subcutaneous tissue 1 (1.38%), external oblique muscle 1 (1.38%), plane between the external and internal oblique muscles 5 (6.94%), internal oblique muscle 26 (36.1%), transversus abdominis muscle 9 (12.5%), and peritoneum 13 (18%). CONCLUSIONS: We conclude that the needle and local anaesthetic placement using the standard landmark-based approach to the TAP block is inaccurate, and the incidence of peritoneal placement is unacceptably high.

Long-term functional outcome and performance status after intensive care unit re-admission: a prospective survey.

BACKGROUND: Intensive care unit (ICU) re-admission identifies a high-risk group in terms of hospital mortality, length of stay, and resource utilization. Only hospital and ICU mortality are well described in the literature on critically ill patients needing re-admission. METHODS: With ethical committee approval, from a prospectively collected database of all admissions to a combined medical and surgical ICU from January 1 to December 31, 2004, we identified all ICU re-admissions from within the hospital and analysed the factors associated with increased incidence of re-admission. At 2-3 yr after discharge, we evaluated the functional outcome of the surviving re-admitted patients as Glasgow Outcome Score (GOS) and Karnofsky index and identified determinants of both mortality and good functional outcome. RESULTS: Seventy-three (7.4%) of the 1061 patients who survived their first ICU stay were re-admitted during the study period. Of the 73 re-admitted patients, 14 died in ICU, 17 died later in the same hospital stay, and 10 died in the interim. Thus, 32 (43.8%) were alive 2-3 yr after discharge. The median [IQR] GOS of the survivors was 4 (see Mackle and colleagues in One year outcome of intensive care patients with decompensated alcoholic liver disease. CONCLUSIONS: Although the ICU, hospital, and subsequent mortalities are high in patients after ICU re-admission, most survivors at 2-3 yr had by then made a good functional recovery and were independent.

New lessons: Classic treatments in convulsive status epilepticus.

Convulsive status epilepticus is a relatively common life-threatening illness requiring prompt intervention. There has been much debate about the appropriate protocol for management of convulsive status epilepticus. Published data on the management of this condition in Ireland is limited. Our aim was to establish if there was a structured, evidence-based or consensus-based protocol being implemented in the management of status epilepticus in our centre. We retrospectively audited all charts with a diagnosis of 'Status Epilepticus' admitted to our hospital from January 1998 to December 2002. A total of 95 episodes of convulsive status epilepticus were recorded. 34 charts were reviewed. Benzodiazepines were the drug class of first choice in 96% of patients. However, the doses of benzodiazepines used varied widely. The most frequent dose of phenytoin used was 1 gram. No one received continuous EEG monitoring during treatment of refractory status epilepticus. Overall mortality was 18%. The results of this study show that there is no consistent protocol was being followed for the management of convulsive status epilepticus in our centre. The drugs of first choice varied between diazepam and lorazepam in most cases. Although phenytoin was used as second line drug, the dose used was frequently suboptimal. We have developed a protocol for the management for convulsive status in our centre.